Antimicrobial-resistant organisms (AROs) are endemic in nursing homes (NH) with prevalence rates surpassing those in hospitals. The basic question of interaction between a disabled host, institutional environment, and caregiver contact in ARO acquisition (and transmission) remains unanswered. We hypothesize that specific activities of daily living (ADL) disability patterns in NH residents will predict acquisition risk or new AROs. We will examine whether disability and risk of acquisition are proportional to healthcare worker contact time and contact intensity. Our proposed Specific Aims are: Aim 1: Develop and examine a risk-stratification model utilizing resident-, HCW-, and environmental-level factors to identify three categories of NH residents: (1) never acquire an ARO; (2) intermittently acquire an ARO; and (3) newly acquire an ARO and remain persistently colonized. Resident-level factors include incremental levels and specific patterns of ADL impairment, presence of wounds, and use of indwelling devices. HCW factors include contact time and intensity, as well as varying levels of nursing resource utilization. The environment factors include presence of AROs on inanimate objects in resident rooms, common areas, and rehabilitation rooms. We will also establish a molecular fingerprint between the strains of AROs colonizing functionally-impaired residents and those isolated from their environment and the hands of caregivers. Using this risk-stratification model, we will establish the optimal ARO prevention strategy in highest-risk functionally-disabled NH residents. Aim 2: Design and evaluate the effectiveness of a multi-component intervention to reduce new acquisition of AROs in the highest-risk functionally-disabled NH residents. This intervention will incorporate resident level, environmental, and caregiver-based strategies. The proposed translational study is innovative and timely because it will develop a risk-stratification model to identify functionally-disabled NH residents who are most likely, if colonized, to transmit AROs; define a molecular fingerprint of resident-caregiver-environment ARO contamination; and design and implement a multi-component comprehensive intervention targeting high-risk functionally-disabled residents. The impact of this research will be an effective, efficient, and infection prevention program for NHs to limit ARO acquisition and more importantly transmission. We expect our results to have widespread application in NHs, enhance residents' quality of life, reduce hospital transfers, reduce healthcare costs and shift the evolving paradigm of infection control and prevention in NHs.